Regulatory T (Treg) cells are essential for control of inflammatory processes by suppressing effector T-cell functions. The actions of PGE₂ on the development and function of Treg cells, particularly under inflammatory conditions, are debated. In this study, we employed pharmacological and genetic approaches to examine whether PGE₂ had a direct action on T cells to modulate de novo differentiation of Treg cells. We found that TGF-β-induced Foxp3 expression and iTreg cell differentiation in vitro is markedly inhibited by PGE₂, which was mediated by the receptors EP2 and EP4. Mechanistically, PGE₂-EP2/EP4 signalling interrupts TGF-β signalling during iTreg differentiation. Moreover, EP4 deficiency in T cells impaired iTreg cell differentiation in vivo. Thus, our results demonstrate that PGE₂ negatively regulates iTreg cell differentiation through a direct action on T cells, highlighting the potential for selectively targeting the PGE₂-EP2/EP4 pathway to control T cell-mediated inflammation.

中文翻译：

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前列腺素 E2 通过拮抗 TGF-β 信号传导直接抑制诱导型调节性 T 细胞通过 EP2 和 EP4 受体的转化

调节性 T (Treg) 细胞通过抑制效应 T 细胞功能对控制炎症过程至关重要。PGE ₂对 Treg 细胞发育和功能的作用，特别是在炎症条件下，存在争议。在这项研究中，我们采用药理学和遗传学方法来检查 PGE ₂是否 对 T 细胞具有直接作用以调节 Treg 细胞的从头分化。我们发现TGF-β诱导的体外Foxp3表达和iTreg细胞分化被PGE ₂显着抑制，这是由受体EP2和EP4介导的。机械地，PGE ₂-EP2/EP4 信号在 iTreg 分化期间中断 TGF-β 信号。此外，T 细胞中的 EP4 缺乏会损害体内 iTreg 细胞的分化。因此，我们的结果表明，PGE ₂通过直接作用于 T 细胞负调节 iTreg 细胞分化，突出了选择性靶向 PGE ₂ -EP2/EP4 途径以控制 T 细胞介导的炎症的潜力。